PM2.5暴露对小鼠肝脏能量代谢的影响

通过细颗粒物(particulate matter 2.5,PM_(2.5))的暴露,探讨其对小鼠肝脏能量代谢方式的影响及作用机制.采用透射电镜(TEM)观察肝脏组织中线粒体超微结构的改变,并检测了三磷酸腺苷(ATP)、丙酮酸和乳酸含量的变化,同时用实时荧光定量-聚合酶链式反应(RT-PCR)检测糖酵解相关基因果糖-2,6-二磷酸酶(PFKFB3)和乳酸脱氢酶(LDHB)及三羧酸循环(TCA)相关基因丙酮酸脱氢酶(PDHA1)、柠檬酸合成酶(CS)和延胡索酸酶(FH)的表达情况.此外,还对活性氧(ROS)的水平进行检测.结果表明,PM_(2.5)暴露对小鼠肝脏组织中的线粒体造成损伤,导致ATP的下降,丙酮酸和乳酸的积累.此外,PDHA1、CS和FH的表达明显降低,PFKFB3和LDHB的表达显著升高,这些结果共同表明PM_(2.5)改变了小鼠肝脏的能量代谢方式.同时ROS水平明显升高,表明PM_(2.5)暴露可能是通过ROS抑制三羧酸循环,增强糖酵解方式来为机体提供能量,从而对肝脏的能量代谢产生影响.

Exposure to PM2.5 promotes the conversion of energy metabolism in livers of mice

In the present study, we aimed to study the effect of exposure to particulate matter (PM_2.5) on energy metabolism in mice liver and the mechanism of toxicity. We observed mitochondrial ultrastructure changes in liver tissue by transmission electron microscope (TEM) and detected the content of adenosine triphosphate (ATP), pyruvate and lactate. We also investigated the variations of related genes involved in glycolysis (PFKFB3 and LDHB) and the TCA cycle (PDHA1, CS and FH). In addition, the content of ROS was also detected.The results showed that PM_2.5 can cause mitochondrial damage in liver issue which resulted in the decline of ATP and the accumulation of pyruvate and lactate. Moreover, the expression of PDHA1, CS and FH significantly declined while that of PFKFB3 and LDHB increased obviously. These results together showed that PM_2.5 changed the energy metabolism of liver in the mice. At the same time, the content of ROS increased obviously which indicated that ROS generation partially accounted for the shunting of the energy metabolism induced by PM_2.5 through directly perturbing the activities of several key TCA cycleenzymes and stimulating glycolysis.